Adrenal Insufficiency (AI)

The adrenal glands’ principle responsibility is the secretion of stress hormones which include such corticosteroids as cortisol and catecholamines (i.e.; epinephrine). Adrenal insufficiency is the body’s failure to produce steroid hormones in amounts adequate for the proper regulation of organ function, especially during stressful situations. Note the mention of “the body’s” failure as opposed to the failure of the adrenal glands. This is the key point behind the two main types or categories of adrenal insufficiency:

1) Primary Adrenal Insufficiency: characterized by local (within the adrenal glands) damage or impairment that prohibits sufficient production of hormones such as glucocorticoid (i.e.; cortisol) and mineralocorticoid (aldosterone) by the adrenal cortex (outer layer).

2) Secondary (Central) Adrenal Insufficiency: characterized by the failure of the pituitary or the hypothalamus to produce the hormones (ACTH and CRH respectively) that in turn trigger hormone production by the adrenal glands. In this case, the adrenal cortex may very well be healthy except for the fact that it is not receiving proper stimulation via the hormonal action of either the pituitary or the hypothalamus.

Note: Suboptimal adrenal function (SAF), also variously known as adrenal fatigue, adrenal exhaustion or adrenal burn-out, is occasionally presented as a third category of adrenal insufficiency. However, given that SAF is rooted in lifestyle/stress issues and involves no pathology in the adrenals nor related physiology, I have decided to add a separate page for Suboptimal Adrenal Function.

Primary adrenal insufficiency; Addison’s disease

The original descriptions of “general languor and debility”, “feebleness of the heart’s action”, “irritability of the stomach”, and “a peculiar change of the color of skin” summarizes the dominant features of Addison’s disease. Addison’s disease results from a progressive destruction of adrenal glands over time. Once the destruction involves more than 90% of the adrenal cortex, adrenal insufficiency manifests. Advanced cases of Addison’s disease are usually easy to diagnosis but early stages can be a challenge. Addison’s disease is somewhat rare, can happen at any age, and can affect both sexes.

Causes of primary adrenal insufficiency:

  1. Anatomic destruction of adrenal cortex (chronic or acute) via:
    • Autoimmune (idiopathic) disorders; accounts for 70-90% of cases
    • Surgical removal
    • Hemorrhage (bleeding into adrenal cortex)
    • Invasion by metastatic cancer
    • Infection (viral, bacterial, fungal)
  2. Metabolic failure in hormone production:
    • Congenital
    • Substances that inhibit the function of enzymes important in the synthesis of adrenal hormones
    • Cytotoxic agents

Secondary (central) adrenal insufficiency:

In secondary adrenal insufficiency, the problem does not originate at the adrenals but at the pituitary or the hypothalamus. There are different cells present in the pituitary, each responsible for producing a different hormone (FSH, LH, Prolactin, growth hormone, ACTH). These cells are in turn stimulated by the so called releasing hormones of the hypothalamus. In secondary adrenal insufficiency, pituitary cells responsible for the production of the adrenocorticotropic hormone (ACTH, also known as corticotropin) are deficient in their function.

Causes of central adrenal insufficiency:

  1. Exposure to exogenous glucocorticoids (drugs such as such as cortisone, hydrocortisone, and prednisone administered for the management of pain, inflammation and asthma among other issues) for more than four weeks regardless of route of administration. This is the most common cause of secondary AI
  2. Pituitary tumors: benign (Adenoma)
  3. Pituitary tumors, malignant (somewhat rare)
  4. Tumors arising from metastasis to hypothalamus
  5. Radiation of pituitary gland, areas outside the hypothalamic- pituitary-adrenal axis
  6. As part of Autoimmune Poly Endocrine Syndrome (Autoimmune Thyroid Disease, Primary Gonadal Failure, Type 1 Diabetes, Pernicious Anemia)
  7. Genetic Mutation
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